DESCRIPTION: Dry eye affects six to seven million people in the United States alone. Meibomian gland disease is even more frequent, particularly in older patients. Clinically, patients may express a combination of two forms of dry eye, aqueous deficient and evaporative. Both mechanisms of development of dry eye share the common feature of instability of the tear film with rapid tear break-up time, suggesting there may be a shared structural abnormality of the tear film that is responsible for the instability. Disruption of the normal lipid-protein-aqueous structure of the tear film is probably this mechanical event. Understanding the normal lipid-protein-aqueous structure of the tear film is therefore critical to determine the etiology of the tear film instability due to dry eye disease and meibomian gland disease. Recent advances in spectroscopic technology make it feasible to measure simultaneously and, in individuals without pooling or serial collection, the pool of meibomian lipid on the lid margins, lipids in the meibomian glands, and the lacrimal lipids, many of which are bound to lipocalin or complexed with other proteins found in tears. We propose to use the latest spectroscopic innovations to determine the relationships among tear lipid structure, interactions, rate of tear evaporation, dry eye symptoms and tear film instability. Advances in clinical diagnosis make it possible to group patients into a number of categories related to production-deficient and evaporative forms of dry eye and monitor their tear film stability. Because of our expertise in spectroscopic techniques, knowledge of lipid structure, and access to human tear lipid samples in normal subjects and those with dry eye disease, coupled with our clinical expertise, we are in a uniquely favorable position to identify the nature of the disturbance of the lipid-protein-aqueous interaction of the tear film that could lead to improved therapy.